Insulin-dependent diabetes mellitus (IDDM) incidence varies 6-fold among populations of European origin, with the highest rates in Scandinavia, intermediate in the U.S. and the lowest in Poland. if it were possible to lower the U.S. rate to that in Poland, IDDM would be prevented in 7,000 of an estimated 11,000 children that are diagnosed in the U.S. annually. The main goal of this application is to help to identify the reasons for the excess of IDDM in the U.S., compared to Poland. Specific aims: 1.To set up the radioimmunoassay for human autoantibodies against glutamate decarboxylase (GAD) and to modify an already existing assay against insulin autoantibodies (IAA), in the collaborating laboratory in the Dept of Immunopathology, Academy of Medicine in Poznan, Poland. 2. Establish appropriate quality control procedures based on sample exchange between the laboratories at the Dept of Immunopathology, Academy of Medicine in Poznan and at the Barbara Davis Center for Childhood Diabetes in Denver. 3. Using the GAD and IAA assays, test in the Polish laboratory serum samples collected within this project from: a) 300 young (0-7 years of age) relatives of persons with IDDM in Poland; b) 850 Polish school children aged 2-3 years with no family history of IDDM; and c) 850 Polish young children aged 6-7 years, with no family history of IDDM. 4. Compare the age-specific prevalence (at ages 2-3 and 6-7 years) of GAD and IAA in: a) the low IDDM risk general Polish population and in the high IDDM risk Colorado population b) nondiabetic siblings and offspring of persons with IDDM in Poland and Colorado. These specific aims are parallel to those of the parent U.S. grant (DK- 32493, Rewers M., PI). Availability of the GAD and IAA assays in Poland will allow to test selected parent grant's hypotheses in a population which is at lower IDDM risk than the U.S. population, but where the incidence of IDDM has recently rapidly increased. The investigators have worked together in the past 3 years, on a related project funded from the Marie Curie-Sklodowski Fund (HHS/MCS grant 90-25, Rewers M & Fichna P, PI) that has established, for the first time in the Polish population, the associations of IDDM with HLA-DR alleles and islet cell antibodies. This new proposed project will set the stage for future large-scale screening to collaboratively predict and prevent IDDM using standard protocols.